Quantitative Structure–Cytotoxicity Relationship of Pyrano[4,3-<i>b</i>]chromones

Nagai, Junko; Shi, Huidong; Kubota, Yuka; Bandow, Kenjiro; Okudaira, Noriyuki; Uesawa, Yoshihiro; Sakagami, Hiroshi; Tomomura, Mineko; Tomomura, Akito; Takao, Koichi; Sugita, Yoshiaki

doi:10.21873/anticanres.12747

Cited by 11 publications

(15 citation statements)

References 4 publications

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“…We investigated a total 291 compounds from 17 different groups ( A~Q ) of their cytotoxicity (assessed by CC 50 ) against four human OSCC (Ca9-22, HSC-2, HSC-3, and HSC-4) and three human normal mesenchymal cells (HGF, HPLF, and HPC), and then their tumor specificity (assessed by TS M , calculated as describe in Figure 2 , and potency-selectivity expression (PSE)) [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. PSE, that reflects both tumor specificity and cytotoxicity against tumor cells, was calculated by dividing the TS M by CC 50 for tumor cells, and then multiplying by 100.…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

“…This demonstrated that only limited numbers of compounds show higher tumor specificity, although their structures are very similar with each other. It is possible that such highly tumor-specific compounds show the optimal 3D structure, since the tumor specificity of chromone compounds shows the tight correlation with chemical descriptors that reflect the 3-D structure ( Table 4 ) [ 33 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

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Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

et al. 2020

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Since many anticancer drugs show severe adverse effects such as mucositis, peripheral neurotoxicity, and extravasation, it was crucial to explore new compounds with much reduced adverse effects. Comprehensive investigation with human malignant and nonmalignant cells demonstrated that derivatives of chromone, back-bone structure of flavonoid, showed much higher tumor specificity as compared with three major polyphenols in the natural kingdom, such as lignin-carbohydrate complex, tannin, and flavonoid. A total 291 newly synthesized compounds of 17 groups (consisting of 12 chromones, 2 esters, and 3 amides) gave a wide range of the intensity of tumor specificity, possibly reflecting the fitness for the optimal 3D structure and electric state. Among them, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound 22), which belongs to 3-styrylchromones, showed the highest tumor specificity. 22 induced subG1 and G2 + M cell population in human oral squamous cell carcinoma cell line, with much less keratinocyte toxicity as compared with doxorubicin and 5-FU. However, 12 active compounds selected did not necessarily induce apoptosis and mitotic arrest. This compound can be used as a lead compound to manufacture more active compound.

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Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

et al. 2020

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“…We recently found that the tumor-specificity of 3-(Ncyclicamino)chromone derivatives (29), 2-(N-cyclicamino) chromone (21), pyrano [4,3-b]chromones (30) and furo [2,3b]chromones (31) was also well correlated with descriptors that reflect the molecular shape. The next step of our research is to estimate the structure that should show higher tumor-specificity based on the accumulated QSAR data base, and then synthesize such compound for the Figure 6.…”

Section: Against Four Human Oscc Cell Lines Ca9-22 (•) Hsc-2 (■) Hmentioning

confidence: 99%

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

et al. 2019

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Background/Aim: Studies of biological activity of 2styrylchromone derivatives focusing on antioxidant, antiinflammatory, antiviral and antitumor activity are limited. In this study, eighteen synthetic 2-styrylchromone derivatives were investigated for their cytotoxicity against human malignant and non-malignant cells, and then subjected to quantitative structure-activity relationship (QSAR) analysis. Materials and Methods: Tumor-specificity was calculated by the ratio of mean 50% cytotoxic concentration (CC 50) against four normal oral cells to that against oral squamous cell carcinoma cell lines. Induction of apoptosis and growth arrest were evaluated by cellcycle analysis. For QSAR analysis, 3,117 types of physicochemical, structural, and quantum chemical features were calculated from the most stabilized structure of 2styrylchromone derivatives. Results: Two 2-styrylchromone derivatives in which a methoxy group was introduced at the 4position of the benzene ring showed tumor-specificity equivalent to or higher than doxorubicin in TS value. These compounds accumulated the subG 1 and G 2 /M phase cells, suggesting the induction of apoptosis. Their tumor-specificity can be explained mainly by molecular shape and electronic state. Conclusion: These findings suggest the applicability of 2-styrylchromone to develop safe and effective anticancer agents as seed compounds. Our group recently found that low-molecular weight natural polyphenols, such as tannins and flavonoids showed very low anticancer activity (evaluated by tumor-specificity with human cultured malignant and none-malignant cells) (1). On the other hand, chemical modification of chromone, two ring backbone structure present in flavonoids, yielded derivatives with much higher tumor-specificity (2, 3). 2-Styrylchromone is a derivative having a styryl group bonded to the 2-position of the chromone skeleton. Synthetic 2styrylchromone derivatives have been reported to show radical scavenging (4, 5), anti-inflammatory (6), hepatoprotective (7), neuroprotective (8-10), anti-human immunodeficiency virus (11), anti-norovirus (12), anti-rhinovirus (13, 14), antitumor (15-18), and monoamine oxidase B inhibiting (19) activity. However, very few studies tested their cytotoxicity against normal cells (16). In the present study, we investigated the cytotoxicity of eighteen synthetic 2-styrylchromone derivatives (Figure 1) against four human oral squamous cell carcinoma (OSCC) cells lines (Ca9-22, HSC-2, HSC-3, HSC-4) and three human normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligamental fibroblast (HPLF) and human pulp cell (HPC)], and performed quantitative structure-activity relationship (QSAR) analysis. Materials and Methods Materials.

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“…Chromone (4 H -1-benzopyran-4-one) is a backbone structure of flavonols, flavones, flavanones and isoflavones [29] (Figure 1B). We synthesized eight classes of chromones derivatives (total 134 compounds): 3-styrylchromones (15 compounds) [30,31] (containing compound A), 3-benzylidenechromanones (17 compounds) [32] (containing compound B), 3-styryl-2 H -chromenes (16 compounds) [33] (containing compound C), 2-azolylchromones (24 compounds) [34] (containing compound D), 3-( N -cyclicamino)chromones (15 compounds) [35] (containing compound E), 2-( N -cyclicamino)chromones (15 compounds) [36] (containing compound F), furo[2,3- b ]chromones (12 compounds) [37] (containing compound G) and pyrano[4,3- b ]chromones (20 compounds) [38] (containing compound H). The eight compounds that produced the highest TS value in each group are listed in Figure 4.…”

Section: Chromone Derivatives As New Type Of Anticancer Candidatementioning

confidence: 99%

Recent Progress of Basic Studies of Natural Products and Their Dental Application

et al. 2018

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The present article reviews the research progress of three major polyphenols (tannins, flavonoids and lignin carbohydrate complexes), chromone (backbone structure of flavonoids) and herbal extracts. Chemical modified chromone derivatives showed highly specific toxicity against human oral squamous cell carcinoma cell lines, with much lower toxicity against human oral keratinocytes, as compared with various anticancer drugs. QSAR analysis suggests the possible correlation between their tumor-specificity and three-dimensional molecular shape. Condensed tannins in the tea extracts inactivated the glucosyltransferase enzymes, involved in the biofilm formation. Lignin-carbohydrate complexes (prepared by alkaline extraction and acid-precipitation) and crude alkaline extract of the leaves of Sasa species (SE, available as an over-the-counter drug) showed much higher anti-HIV activity, than tannins, flavonoids and Japanese traditional medicine (Kampo). Long-term treatment with SE and several Kampo medicines showed an anti-inflammatory and anti-oxidant effects in small size of clinical trials. Although the anti-periodontitis activity of synthetic angiotensin II blockers has been suggested in many papers, natural angiotensin II blockers has not yet been tested for their possible anti-periodontitis activity. There should be still many unknown substances that are useful for treating the oral diseases in the natural kingdom.

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Quantitative Structure–Cytotoxicity Relationship of Pyrano[4,3-b]chromones

Abstract: Abstract. (chromone) provides a backbone structure for the chemical synthesis of potent anticancer drugs. Since studies of the biological activity of pyrano [4,3-b]chromones are limited, we investigated a total of 20 pyrano [4,3-b]

Cited by 11 publications

References 4 publications

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

Recent Progress of Basic Studies of Natural Products and Their Dental Application

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